Meta-analysis showed 11% death reduction in tocilizumab RCTs

Among patients hospitalized with Covid-19, treatment with tocilizumab was associated with reduced mortality in a systematic review and meta-analysis. Researchers reported an 11% reduction in mortality among tocilizumab-treated patients in the nine randomized trials included in the analysis, and a 31% mortality reduction associated with the treatment in the observational trials. The meta-analysis findings were reported this week at the annual meeting of the European Respiratory Society–ERS International Congress 2021.

“As of August 10, 2021, more than 204 million individuals have been infected with SARS-CoV2 worldwide and 4,300,000 deaths globally have been attributed to Covid-19. Tocilizumab is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor that has be repurposed againtst the cytokine storm in the setting of Covid-19,” wrote Christos Kyriakopoulos, MD, of the University of Ioannina Faculty of Medicine, Ioannina, Greece, and colleagues.

In late June of this year, the U.S. Food and Drug Administration granted emergency use authorization (EUA) status to tocilizumab for the treatment of hospitalized adult and pediatric Covid-19 patients receiving systemic corticosteroids and requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). This action was taken even though not all studies have shown benefits for tocilizumab in the treatment of hospitalized patients who are critically ill with Covid-19.

In early April, researchers reported findings from the randomized COVACTA trial of tocilizumab involving 438 patients hospitalized with Covid-19 treated at 62 hospitals in Europe and North America. Eligible patients were randomly assigned in a 2:1 ratio to receive a single intravenous infusion of tocilizumab (at a dose of 8 mg/kg, with a maximum dose of 800 mg) or placebo plus standard care.

The trial failed to show significantly better outcomes or lower mortality at 28 days in the tocilizumab-treated patients. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% CI, 1.0-1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0-4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5- 0; P=0.31). Mortality at day 28 was 19.7% in the tocilizumab group compared with 19.4% in the placebo group (weighted difference, 0.3 percentage points; 95% CI, –7.6 to 8.2; nominal P=0.94).

Conversely, in the international REMAP-CAP randomized trial involving critically ill Covid-19 patients receiving organ support, treatment with tocilizumab was found to be associated with improved outcomes, including survival.

The newly reported meta-analysis included data from both the REMAP-CAP and COVACTA studies, along with seven other randomized clinical trials (RCTs) including RECOVERY, which included 2,094 patients in the tocilizumab analysis. Just over 27,000 patients were involved in all the studies included in the analysis, including 8,048 (29.8%) treated with tocilizumab.

In 39 studies, corticosteroids were concomitantly given, including eight of the nine randomized trials and 31 observational studies. Among the main findings:

  • In both RCTs and observational studies, and use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio, RR, 0.89, 95% CI 0.82 to 0.96; I2=0.3%) 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83; I2=84.0%).
  • The need for invasive mechanical ventilation was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93); a non-significant 19% reduction was seen in observational studies.
  • Both RCTs and observational studies showed a benefit for tocilizumab on the composite endpoint of mortality or invasive mechanical ventilation (RCTs: 17% reduction; observational studies: 45% reduction).
  • The composite endpoint of ICU admission or invasive mechanical ventilation was reduced by 20% in RCTs, while no difference between the two treatment groups was seen in the observational studies.

In the three RCTs and nine observational studies reporting results for the median duration of hospitalization, no differences were seen in the length of hospitalization between the two groups. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while there was a trend in favor of the concomitant use in the RCTs.

Treatment with tocilizumab was associated with mortality reductions in both non-ICU (31%) and ICU (25%) patients (RR 0.69 and 0.75, respectively).

  1. Among patients hospitalized with Covid-19, treatment with the anti-IL-6 receptor monoclonal antibody tocilizumab was associated with reduced mortality in a systematic review and meta-analysis.

  2. Researchers reported an 11% reduction in mortality among tocilizumab-treated patients in the 9 randomized trials included in the analysis and a 31% mortality reduction associated with the treatment in the observational trials.

Salynn Boyles, Contributing Writer, BreakingMED™

The researchers declared no funding source for this analysis, nor relevant disclosures.

Cat ID: 203

Topic ID: 98,203,501,521,728,791,932,190,926,192,927,925,934,203